The World Health Organization (WHO) has declared overweight as one of the top ten risk conditions in the world and one of the top five in developed nations (WHO). In most populations, the prevalence of overweight and obesity has steadily increased over the past 20 years (Vasan, R S et al., 2005). As such, increasing relative weight trends in populations have caused much concern among health care providers (Hill J O et al., 2003). Given the growing prevalence of overweight and related health consequences, there is a critical need for affordable and effective weight management strategies.
As a non-invasive primary treatment strategy for overweight and obesity, reduced-energy diets (appetite suppression) are a widely-recommended approach. Using data from national surveys, it was estimated that affecting energy balance by 100 kilocalories per day (e.g. ˜4% of daily energy intake), weight gain in most of the US population could be prevented (Hill et al, 2003). It is in this context that ingredients that are designed to affect mechanisms regulating satiety may play a role, especially if these could be incorporated into every day foods.
Gastrointestinal signals are crucial for the regulation of food intake, satiety and satiation. Satiety feelings on a meal-to-meal basis are to a large extent determined by a coordinated series of neural and humoral signals that originate from the gut in response to mechanical and chemical properties of ingested food (Woods S C et al., 2004).
An option to prolong satiety and to reduce food intake is by delaying gastric emptying and/or small intestinal transit time (Geliebter A et al., 1988) (Jones K L et al., 1997) (Hveem K et al., 1996). This may be achieved by activation of the ileal brake (Van Citters G W et al., 1999). The ileal brake is the primary inhibitory distal-to-proximal feedback mechanism that controls meal transit through the gastrointestinal tract and is thought to regulate and optimize nutrient digestion and absorption (Van Citters G W et al., 1999).
It has been demonstrated that postprandial infusion of a small amount of fat into the ileum reduces hunger and increases satiety. Presence of fat in small intestine is associated with modulation of gastric emptying (Heddle R et al., 1989), and gastrointestinal hormone secretion (Macintosh C G et al., 1999), including CCK from the proximal (Buffa R et al., 1976), and peptide YY (PYY) from the distal (Adrian T E, et al., 1985), small intestine. Fat in the (distal part of the) small intestine also has the capacity to suppress appetite and energy intake (Chapman I M et al., 1999).
Several studies have shown that direct delivery of lipids into the ileum delays gastric emptying, (Welch I M et al., 1988), prolongs small intestinal transit time (Read N W et al., 1984) and induces satiety (Welch I et al., 1985).
Long-chain fatty acids are potent triggers of the ileal brake, (Van Citters G W et al., 1999) (Read N W et al., 1984), and several studies have demonstrated that the ileal brake is already activated by small amounts of fat or free fatty acids (Keller J et al., 2006) (Pironi L et al, 1993) (Dobson C L et al., 1999). The effects of free fatty acids on gastrointestinal function, including motility, hormone release, and energy intake (Feltrin K L et al., 2004) (Hunt J N et al., 1968) (Matzinger D et al., 2000) (McLaughlin J et al., 1999), also are dependent on their acyl chain length. Hunt and Knox (Hunt J N et al., 1968) were the first to demonstrate that fatty acids with a chain length of 12 and more carbon atoms empty from the stomach much slower than fatty acids containing 10 or fewer carbon atoms.
The mechanisms by which long fatty acid chain (>C12) inhibits subsequent energy intake are unclear. There is some evidence that the effects of long chain fatty acids are dependent on the release of CCK (Lal S et al., 2004); for example, the inhibitory effects of C12 on gastric emptying and the perception of intragastric volume are attenuated by the CCK1 receptor antagonist loxiglumide (Lal S et al., 2004). The effects of fatty acids also appear to involve the activation of vagal afferents, either directly or via CCK (Cox J E et al., 2004) (Lal S et al., 2001). The effects of C12 on energy intake may also be mediated through the actions of GLP-1 (Feltrin K L et al., 2004), and possibly other peptides, and by the changes in gastrointestinal motility, perhaps particularly the stimulation of pyloric motility (Xu X et al., 2005).
Fat Metabolism
Most dietary lipids are absorbed in the proximal two thirds of the jejunum. Normally, more than 94 percent of dietary fat is absorbed. Dietary lipids, consisting mostly of triglycerides, must be emulsified to expose a large surface area to lipolytic enzymes. Emulsification begins in the upper gastrointestinal tract through mastication and gastric mixing. Fat droplets released by these mechanical means are coated with phospholipids to form a stable emulsion. Ingested phospholipids (mostly phosphatidylcholine) exist in a ratio to triglycerides of approximately 1:30, which is adequate for coating. Additional phospholipid from bile is added once the emulsion reaches the duodenum.
Fat hydrolysis begins in the stomach by the actions of lingual lipase, and gastric lipase. Free fatty acids released by gastric lipolysis contribute to the stimulation of pancreatic lipase and colipase, which are responsible for the majority of lipid hydrolysis.
The lipid emulsion in the duodenum is then exposed to pancreatic lipase and degraded to monoglycerides and fatty acids. In this form the lipids are solubilised into small lipid particles also known as mixed micelles, consisting of phospholipids and bile. These mixed micelles transport the free fatty acids and monoglycerides to the intestinal wall, where the lipids are absorbed over the intestinal wall.
Despite great progress in the identification of central signals that regulates satiety, and considerable investment in the development of appetite-controlling medications, improvements are required.